Chemical indicator sheets and packaging bags for sterilization made with the use of the same

ABSTRACT

This invention provides a sheet which has a chemical indicator, in particular, a composition layer for use as an indicator in hydrogen peroxide plasma sterilization, and further provides a packaging bag for said sterilization with use of such an indicator. Said composition layer comprises both a dye which can change color when contacted with hydrogen peroxide vapor or plasma derived from hydrogen peroxide, and a certain organic amine compound.

This is U.S. national phase under 35 U.S.C. §371 of InternationalApplication PCT/JP98/01735, filed Apr. 16, 1998.

TECHNICAL FIELD

This invention relates to a chemical indicator, in particular, a sheethaving a composition layer which is useful in a hydrogen peroxide plasmasterilization treatment, and to a packaging bag for such a plasmasterilization treatment which has said composition layer.

BACKGROUND ART

Since long ago, various kind of sterilization means have been applied toarticles of every species such as disposable or recyclable medicalapparatuses and food containers, and there have also been proposedindicators for conveniently distinguishing whether such a sterilizationtreatment has been made or not. For example, Japanese Patent ApplicationLaid-Open (Kokai) No. 36172/1984 discloses an indicator for gassterilization treatment with use of ethylene oxide; and Japanese PatentApplication Laid-Open (Kokai) Nos. 287972/1986, 43827/1993 and65441/1993 each disclose an indicator ink for electron beamsterilization. The latter group of Laid-Open (Kokai) Applications eachmention an indicator wherein a pH indicator is used in combination withsuch a high molecular compound as is capable of generating hydrogenchloride when irradiated with electron beam.

On the other hand, as a means to conduct a sterilization treatmentwithout adversely affecting medical equipments which are produced fromvarious materials, there have recently been proposed and put intopractice a hydrogen peroxide plasma sterilization method and anapparatus therefor (See: Japanese Patent Publication (Kokoku) Nos.62261/1990 and 22693/1995). This sterilization method summarilycomprises a step of contacting an article to be sterilized, withhydrogen peroxide vapor under reduced pressure in an air-tight chamber,and then generating hydrogen peroxide plasma. This method can be said tobe a very useful one, not only in that high sterilization efficiency isattained but also in that, when plasma state is ended, hydrogen peroxideis converted into water and oxygen which are quite harmless.

The above-mentioned Japanese Patent Publication (Kokoku) No. 22693/1995discloses a liquid-dispensing cassette to be used in a plasmasterilization apparatus which cassette is equipped with a cell forcontaining a hydrogen peroxide solution. It is further disclosed thatsaid dispensing cassette may be equipped with an indicator strip havinga color tone with which to detect the leakage of hydrogen peroxidesolution from the liquid-containing cell. Said Publication does notconcretely disclose, however, how to constitute the indicator strip.

Also in putting a hydrogen peroxide plasma sterilization method intopractice, it would be desirable that there should be available such anindicator which can easily distinguish whether or not a sterilizationtreatment has been given to an article to be sterilized, as is employedin the aforementioned gas sterilization treatment with use of ethyleneoxide or electron beam sterilization treatment. Thus, the object of thisinvention is to provide both a sheet having a chemical indicatorcomposition layer (or an indicator function layer) which can distinguishwhether or not a hydrogen peroxide plasma sterilization treatment hasbeen given to an article to be sterilized, and a packaging bag forplasma sterilization having said composition layer.

DISCLOSURE OF INVENTION

The aforementioned Japanese Patent Application Laid-Open (Kokai) No.65441/1993, for example, suggests that, when bisphenols and a substancesuch as triphenylsulfonium hexafluorophosphate which generates acid orfree radical when irradiated with electron beam are compounded with anindicator ink which comprises a pH indicator and such a high molecularcompound as generates hydrogen chloride when irradiated with electronbeam, there can be improved the color changeability of said ink whenirradiated with electron beam. The inventors of the present invention,on the other hand, have found out that, when a dye belonging to aspecific pH indicator is brought into contact with a system whichcomprises hydrogen peroxide and plasma derived from hydrogen peroxideand which does not generate hydrogen chloride, there occurs a certaincolor change, which can be both stabilized and rendered distinct when acertain organic amine is made to co-exist.

Thus, in order to achieve the above-mentioned object, this inventionprovides a sheet used for distinguishing whether a hydrogen peroxideplasma sterilization treatment has been made or not, which sheet has, onits substrate, an indicator composition layer and, under circumstances,an overcoat layer which is provided on said indicator composition layer,the indicator composition layer containing a dye which can change itscolor when contacted with at least one substance selected from the groupconsisting of hydrogen peroxide and plasma derived from hydrogenperoxide, an organic amine compound which does not evaporate underambient conditions, aliphatic alcohol(s) and a synthetic resin which issoluble in said alcohol(s).

This invention which has the aforementioned features makes it possibleto clearly distinguish whether medical apparatuses, food containers andthe like have undergone or not such a hydrogen peroxide plasmasterilization treatment, even after a certain time has passed from saidtreatment.

DETAILED DESCRIPTION OF INVENTION

As for the dye, in the indicator composition layer of this invention,which can change its color when contacted with at least one substanceselected from the group consisting of hydrogen peroxide and plasmaderived from hydrogen peroxide, there can be employed dyes of any kindso long as they make it possible, owing to tr change in color before andafter said contact, to clearly distinguish whether such a contact hasbeen made or not. As typical examples of such dyes, there can be taken,not restrictively, pH indicators which have a transition interval in arange of pH 5.5 to 9.0. Concrete examples of such pH indicators include1,2-dihydroxy anthraquinone (pH 5.5-6.8); dibromothymol sulfonphthalein(Bromothymol Blue: pH 6.0-7.5);5,8-quinolinequinon-8-hydroxy-5-quinolyl-5-imide (pH 6.0-8.0);3-amino-6-dimethylamino-2-methylphenazine hydrochloride (pH 6.8-8.0);phenolsulfonphthalein (Phenol Red pH 6.8-8.4); o-cresolsulfon phthalein(Cresol Red: pH 7.2-8.8); m-cresolsulfon phthalein (pH 7.4-9.0) and thelike, and tr derivatives. In practical use, two or more of theseindicators may be combined with one another.

This invention is characterized in that the above dye is used along withan organic amine compound which does not evaporate under ambientconditions (concretely, at a room temperature at which the sterilizationtreatment is made). Any kind of such organic amine compounds are usableso long as they do not evaporate throughout sterilization treatment, inparticular a low temperature sterilization treatment with use ofhydrogen peroxide (See: for example, Japanese Patent Publication(Kokoku) No. 62261/1990; Thus cited, this Publication constitutes a partof the present invention), and so long as they can adjust pH of thecomposition to alkaline side. Examples of such organic amine compoundsinclude mono higher aliphatic amine such as laurylamine, mono hydroxyhigher aliphatic amine, triethanol amine, diethanol amine andmonoethanol amine. Among these, triethanol amine is preferably employedin particular, in consideration of compatibility with the dye used inthis invention and compatibility with synthetic resin which may beincluded as vehicle in the composition.

The indicator composition layer of this invention can usually contain avehicle (including synthetic resin, solvent, and, if necessary,plasticizer as well), which is normally used for the preparation ofprinting ink, and additive (such as dispersant, stabilizer andthickening agent), and, further, in particular, aliphatic alcohol(s) anda synthetic resin which is soluble in said alcohol(s), for example,polyamide resin.

As for typical example of such synthetic resin, polyamide resin which isnormally used for the preparation of printing ink is convenientlyemployed. As for solvent, isopropyl alcohol, n-propyl alcohol, n-butylalcohol, etc. can be used. Concrete examples of polyamide resin includesuch a polyamide resin as is produced by polycondensation of aliphaticdicarboxylic acid and aliphatic diamines each of which has an averagemolecular weight of 10,000 to 50,000. Typical examples of such resin onthe market include polyamide resins which are being sold by SanwaChemical K.K. under trade names such as SUNMIDE 611DK-1, by Sanyo KaseiK.K. under trade names such as POLYMIDE S-40E and by Toyama Kasei K.K.under trade names such as TOMIDE 395, respectively. These resins may beused either singly or in combination of two or more thereof

The above-mentioned composition may comprise 0.3-10% by weight of dye,3-30% by weight of organic amine compound, 10-60% by weight of aliphaticalcohol, 15-45% by weight of polyamide resin, and, under circumstances,0.3-10% weight of ultraviolet light absorber as well, each on the basisof the total weight of the composition.

In this invention, chemical indicator composition layer may be formed ona substrate to give an indicator-function layer, and, undercircumstances, an overcoat layer may be provided on saidindicator-function layer. The overcoat layer may be formed from anycomponents so long as the resulting layer is permeable to hydrogenperoxide vapor or plasma derived from hydrogen peroxide, and so long assaid formed layer is transparent or semi-transparent such that the colorchange of dye can be seen through. In view of adhesion with indicatorfunction layer, however, the overcoat layer is preferably formed from acomposition which contains those components to form theindicator-function layer, except dye but including ultraviolet lightabsorber instead, and, under circumstances, further including 0.3-10% byweight of wax (e.g., polyethylene wax) on the basis of the total amountof the composition. The formation of overcoat layer can in particularprevent physical injury of indicator-function layer.

As for ultraviolet light absorber, those of any species may be employedso long as they are normally used in this field and unless they haveadverse effects in view of achievement of the object of this invention.For example, benzotriazole derivatives on the market are preferablyused. Typical examples of said derivatives include Tinuvin typecompounds having sunscreen property produced by Ciba-Geigy, which are tobe employed singly or in combination of two or more of them.

The sheet comprising thus formed two layers may either take a strip-likeform or constitute a part of a packaging bag for packing articles to besterilized.

As another embodiment therefore, the present invention provides apackaging bag with an indicator for sterilizing its contents withhydrogen peroxide plasma, wherein there is deposited, on at least a partof said packaging bag, a composition layer for use as a chemicalindicator which comprises both a dye which can change its color whencontacted with at least one substance selected from the group consistingof hydrogen peroxide and plasma derived from hydrogen peroxide, and anorganic amine compound which does not evaporate under ambientconditions, and wherein at least a part of said packaging bag is made ofbreathing sheet.

The packaging bag of the present invention is at least partlyconstituted of breathing material. As for breathing sheet, there ispreferably employed a material which is impermeable to microorganisms,has heat sealability and breathability (preferably of at most 100seconds; JIS-P-8117), and is resistant to hydrogen peroxide and plasmaderived from hydrogen peroxide both of which are main components ofsterilizing gas. Examples of such a material include non-woven fabricmade from high density polyethylene, polypropylene, and the like. It ispreferable in particular to use TYVEK, a non-woven fabric of highdensity polyethylene which is sold by DuPont Japan Limited.

The other portions of the above packaging bag may be constituted of acomposite laminate sheet which is prepared by laminating heat-sealablefilms such as low density polyethylene, polypropylene, and the like, ona polyester film or the like as a base material. The use of such filmsmakes it possible to see contents through the bag.

Such a packaging bag is made in the following manner: (i) as a usualprocess, both a breathing sheet such as non-woven fabric and a plasticfilm laminate sheet are heat-sealed at necessary end portions; (ii) alaminate sheet is folded down, and two ends are made to face each other,and, then, a breathing sheet is placed over the gap between said twoends, and, then, necessary portions are heat-sealed; or (iii) abreathing sheet is employed for bottom of a self-supporting bag.

The indicator-function layer is normally formed on the surface of abreathing sheet. When packaging bag is so transparent as to show itsinterior, indicator-function layer may be formed either on the innerside of breathing sheet, or on the inner side of laminate sheet, i.e.,inside the packaging bag. In this case, however, attention should bepaid so that contents may not be contaminated.

The above-mentioned composition layer of this invention is homogenizedby such a known kneading method as is employed for the preparation ofprinting ink, and is then deposited on a substrate by an also knownprinting method, e.g., offset printing, flexographic printing or gravureprinting, to form an indicator-function layer, and, subsequently, undercircumstances, an overcoat layer is formed, and, thus, the sheet of thisinvention can be produced. The amount of indicator-function layeradhered is, although not restricted, generally 2-20 g/m², preferably3-15 g/m². When the amount adhered is less than 2 g/m², color changeafter treatment is apt to be difficult to be confirmed, while, when itexceeds 20 g/m², scratches are liable to be formed during transportationor storage.

EXAMPLES

In the following, this invention is explained in more detail withconcrete examples. Percentage in the examples mean “% by weight” unlessotherwise specified.

Example 1

Formation of Indicator-function Layer and Overcoat Layer

A composition having the following components:

POLYMIDE S-40E  20.0 (%) (a polyamide resin made by Sanyo Kasei K. K.)Isopropyl alcohol  47.0 n-Propyl alcohol  20.0 Triethanol amine  10.0Phenol Red (including no acid)  2.0 Tinuvin 328  1.0 (an ultravioletlight absorber produced by Ciba-Geigy) Total 100.0

was mixed and kneaded by an enclosed ball mill until the compositionbecame homogeneous, and, thus, a composition for indicator was prepared.

Apart from the above, a composition having the following components:

POLYMIDE S-40E  20.0 (%) Isopropyl alcohol  46.5 n-Propyl alcohol  20.0Triethanol amine  10.0 Tinuvin 328  1.0 Polyethylene wax  2.5 Total100.0

was treated in the same manner as in the above composition forindicator, and, thus, a composition for overcoat was prepared.

Example 2

Preparation and Evaluation of Chemical Indicator

The composition for indicator and the composition for overcoat both ofwhich had been prepared in accordance with Example 1 were placed on thesurface of a non-woven fabric of high density polyethylene by gravuremethod with use of a gravure roll. The amount of the composition forindicator adhered (solid) and the amount of composition for overcoatadhered (solid) are shown together in Table 1.

As for evaluation, the above-mentioned non-woven fabric was put inSTERRAD-100 (LOW Temperature Plasma Sterilization System by Johnson &Johnson Medical Co.), and was subjected to sterilization treatment for75 minutes, and, thus, the degree of color change of the indicator layerby was visually observed. Moreover, said non-woven fabric was irradiatedwith ultraviolet light for 30 minutes with use of Sunshine-typeWeather-Ometer produced by Suga Tester K.K., and, thus, the degree ofcolor change of the indicator layer was visually observed. The resultsare shown together in Table 1.

Evaluation was made according to the following standard:

(Color Changeability)

∘--- Changed to slightly red-tinted yellow or to light yellow

⊚--- Changed to yellow

(Weatherability)

∘--- Although slightly faded, practically no problem.

⊚--- Not added at all.

TABLE 1 Amount of Amount of indicator overcoat Sample adhered adheredColor No. (g/m²) (g/m²) changeability Weatherability (This invention) 14 1 ⊚ ∘ 2 6 1 ⊚ ∘ 3 8 2 ⊚ ⊚ 4 10  2 ⊚ ⊚ (Comparison) 1 1 1 X ∘*1) 2 25 1 ⊚ ∘*2) *1) Color change was hard to confirm. *2) Printed surface wasinjured, and indicator dropped off.

Example 3

Effects of Sterilization Treatment, and Color Change of Indicator

There was applied, by gravure method, 15 g (wet)/m² of the indicator inkof this invention on one surface of a non-woven fabric of high densitypolyethylene. Then, said non-woven fabric with an indicator wassuperposed on a laminate sheet composed of a polyester film as outsidefilm and a low density polyethylene film as inside film, and three sideswere heat-sealed to give a sterilizing bag. Into this sterilizing bag,there were put a 50 ml plastic syringe and a biological indicator (BI),which were then sterilized by means of STERRAD-100 (LOW TemperaturePlasma Sterilization System by Johnson & Johnson Medical Co.) for 75minutes. Said BI, for which a test pack of sporangium (StandardMicroorganism No. ATCC 9372) had been employed, was taken out in agerm-free manner after sterilized by the above-mentioned Low TemperaturePlasma Sterilization System, and was then planted on a sterilized TSBmedium. After culturing at 35° C. for seven days, it was visuallyconfirmed whether any microorganism had grown. It was found resultantlythat the color of the indicator applied on the non-woven fabric hadchanged from reddish violet (before sterilization) to yellow (aftersterilization), and also that BI showed no growth of microorganism. Itwas confirmed from the above facts that it can be distinguished, at thetime when the sterilizing bag of this invention is opened, whetherpacked articles such as medical instruments have undergone asterilization treatment or not.

Industrial Applicability

This invention provides a sheet which has thereon a composition layerwhich makes it possible to clearly distinguish whether packed articlessuch as medical instruments have undergone a sterilization treatment ornot, and further provides a packaging bag for medical instruments whichbag has, in at least a part thereof, such a composition layer asmentioned above. Hence, this invention is applicable both in the fieldof medical treatment and in the field of the production of medicalinstruments.

What is claimed is:
 1. A sheet used for monitoring the efficacy of ahydrogen peroxide plasma sterilization treatment, said sheet comprisingan indicator-function layer, said indicator-function layer comprising: adye which can change color when contacted with at least one substanceselected from the group consisting of hydrogen peroxide and plasmaderived from hydrogen peroxide, an organic amine compound which does notevaporate under ambient conditions, at least one aliphatic alcohol, anda synthetic resin which is soluble in said alcohol.
 2. The sheet ofclaim 1, further comprising an overcoat layer which is provided on saidindicator-function layer.
 3. A sheet used for monitoring the efficacy ofa hydrogen peroxide plasma sterilization treatment, said sheetcomprising: an indicator-function layer comprising: a dye which canchange color when contacted with at least one substance selected fromthe group consisting of hydrogen peroxide and plasma derived fromhydrogen peroxide; an organic amine compound which does not evaporateunder ambient conditions: at least one aliphatic alcohol: a syntheticresin which is soluble in said alcohol; and an overcoat layer which isprovided on said indicator-function layer, said overcoat layercomprising: at least one aliphatic alcohol, a synthetic resin which issoluble in said alcohol, ultraviolet light absorber, and waxes.
 4. Thesheet of claim 1 wherein the aliphatic alcohol(s) is C₃₋₅ alcohol(s) andwherein the synthetic resin is polyamide resin.
 5. A packaging bag forsterilizing its contents with hydrogen peroxide plasma, wherein there isdeposited, on at least a part of said packaging bag, a composition layerfor use as a chemical indicator which comprises both a dye which canchange its color when contacted with at least one substance selectedfrom the group consisting of hydrogen peroxide and plasma derived fromhydrogen peroxide, and an organic amine compound which does notevaporate under ambient conditions, and wherein at least a part of saidpackaging bag is made of breathing sheet.
 6. The packaging bag of claim5 wherein the composition layer for use as a chemical indicator furthercontains aliphatic alcohol(s) and a synthetic resin which is soluble insaid alcohol(s) as well.
 7. The packaging bag of claim 5 wherein thecomposition layer for use as a chemical indicator is deposited in theform of a thin layer on one side of the breathing sheet.
 8. Thepackaging bag of any one of claims 5 wherein the breathing sheet is madeof nonwoven fabric produced from high-density polyethylene orpolypropylene.